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The Journal of Neuroscience, December 15, 2002, 22(24):10935-10940

Attenuation of Nicotine-Induced Antinociception, Rewarding Effects, and Dependence in µ-Opioid Receptor Knock-Out Mice

Fernando Berrendero¹, Brigitte L. Kieffer², and Rafael Maldonado¹

¹ Laboratori de Neurofarmacologia, Facultat de Ciéncies de la Salut i de la Vida, Universitat Pompeu Fabra, 08003 Barcelona, Spain, and ² Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Médicale/Université Louis Pasteur, BP 163 67404 Illkirch, France

The involvement of µ-opioid receptors in different behavioral responses elicited by nicotine was explored by using µ-opioid receptor knock-out mice. The acute antinociceptive responses induced by nicotine in the tail-immersion and hot-plate tests were reduced in the mutant mice, whereas no difference between genotypes was observed in the locomotor responses. The rewarding effects induced by nicotine were then investigated using the conditioning place-preference paradigm. Nicotine produced rewarding responses in wild-type mice but failed to produce place preference in knock-out mice, indicating the inability of this drug to induce rewarding effects in the absence of µ-opioid receptors. Finally, the somatic expression of the nicotine withdrawal syndrome, precipitated in dependent mice by the injection of mecamylamine, was evaluated. Nicotine withdrawal was significantly attenuated in knock-out mutants when compared with wild-type mice. In summary, the present results show that µ-opioid receptors are involved in the rewarding responses induced by nicotine and participate in its antinociceptive responses and the expression of nicotine physical dependence.

Key words: nicotine; opioid; knock-out mice; withdrawal; conditioning place preference; reward

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Copyright © 2002 Society for Neuroscience  0270-6474/02/222410935-06$05.00/0

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